Modified bio-related substance, process for producing the same, and intermediate

Abstract

A modified bio-related substance, wherein at least one poly(alkylene glycol)oxy group represented by the following formula (1) is combined in a molecule: wherein R is a hydrocarbon group having 1 to 24 carbon atoms, OA 1 and OA 2 are each an oxyalkylene group having 2 to 4 carbon atoms, the groups represented by R are the same or different from each other in one molecule, and the groups represented by OA 2 are the same or different from each other in one molecule, n and m are each average number of moles of the oxyalkylene group added, n represents 0 to 1000, and m represents 10 to 1000.

1. A process for producing a polyalkylene glycol derivative of the formula (11), comprising the following step (AA):
 Step (AA): a step of subjecting a compound represented by the formula (10) to a hydrogenative reduction reaction under a condition that a water content in a reaction system is 1% or less: 
 
       
         
           
           
               
               
           
         
       
       wherein G is a residual group of a compound having 2 to 4 hydroxyl groups; R 2  is a hydrocarbon group having 1 to 4 carbon atoms; m1, m2, and m3 represent each average number of moles of an oxyethylene group added and satisfy the following relationship:
   0 ≦m 1≦1000, 0 ≦m 2≦1000, 0 ≦m 3≦1000, 10 ≦m 1 +m 2 +m 3≦1000;
 
 X 1  is an amino group, a carboxyl group, or a protected group thereof; and g1, g2, and g3 represent each an integer and satisfy the following relational equations:
   1 ≦g 1≦3, 0 ≦g 2, 0 ≦g 3, 2 ≦g 1 +g 2 +g 3≦4.
 
 
 
     
     
       2. A process for producing a polyalkylene glycol derivative of the formula (11) according to  claim 1 , wherein in the step (AA), palladium is used as a hydrogenative reduction catalyst, palladium is added in an amount of 1 to 20 wt % based on the compound of the formula (10), and the reaction is carried out at a temperature of 40° C. or lower. 
     
     
       3. A process for producing a polyalkylene glycol derivative of, the formula (16), wherein the following steps (BB1) and (BB2) are carried out:
 Step (BB1): a step of adding a dehalogenating agent and a compound represented by the formula (14) to a compound represented by the formula (12) and reacting them at 20 to 60° C. to obtain a compound of the formula (13), provided that each charged molar ratio satisfies the following relationship:
     Vj≧ 1.5 ×Vh×g 5 
     Vi>Vj    
 
 Vh: number of moles of the compound represented by the formula (12) 
 Vi: number of moles of the dehalogenating agent 
 Vj: number of moles of the compound represented by the formula (14); 
 Step (BB2): a step of adding a compound represented by the formula (15) to the compound of the formula (13) and reacting them at 20 to 80° C. to obtain a compound of the formula (16), provided that each charged molar ratio satisfies the following relationship:
     Vk>Vj    
 
 Vk: number of moles of the compound represented by the formula (15): 
 
       
         
           
           
               
               
           
         
         wherein G is a residual group of a compound having 2 to 4 hydroxyl groups; R 2  is a hydrocarbon group having 1 to 4 carbon atoms; m1, m2, and m3 represent each average number of moles of an oxyethylene group added and satisfy the following relationship:
   0 ≦m 1≦1000, 0 ≦m 2≦1000, 0 ≦m 3≦1000, 10 m 1 +m 2 +m 3≦1000;
 
 
         X 1  is an amino group, a carboxyl group, or a protected group thereof; g4, g5, and g6 represent each an integer and satisfy the following relational equations:
   0 ≦g 4, 1 ≦g 5≦3, 0 ≦g 6, 2 ≦g 4 +g 5 +g 6≦4;
 
 
         W is a halogen atom selected from Cl, Br and I; R 3  is a hydrocarbon group having 1 to 10 carbon atoms; and M is potassium or sodium. 
       
     
     
       4. The process for producing a polyalkylene glycol derivative of the formula (16) according to  claim 3 , comprising a step (BB3) as a successive step of the step (BB2):
 Step (BB3): a step of filtrating the reaction liquid or washing the reaction liquid with an aqueous inorganic salt solution having a concentration of 10 wt % or more. 
 
     
     
       5. The process for producing a polyalkylene glycol derivative of the formula (16) according to  claim 4 , wherein the steps (BB1) to (BB3) are repeated after the step (BB3).